Polarly Localized EccE 1 Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis

Abstract

Tuberculosis (TB), the world’s leading cause of death of humans from an infectious disease, is caused by the intracellular bacterium Mycobacterium tuberculosis . The development of successful strategies to control TB requires better understanding of the complex interactions between the pathogen and the human host. We investigated the contribution of EccE 1 , a membrane protein, to the function of the ESX-1 secretion system, the major virulence determinant of M. tuberculosis . By combining genetic analysis of selected mutants with eukaryotic cell biology and proteomics, we demonstrate that EccE 1 is critical for ESX-1 function, secretion of effector proteins, and pathogenesis. Our research improves knowledge of the molecular basis of M. tuberculosis virulence and enhances our understanding of pathogenesis.